Okay. Welcome everybody to the forty-second annual JP Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by my squad, Malcolm Kuno, Priyanka Grover, and Lyra Hall. Our next presenting company is Amicus, and presenting on behalf of the company, we have CEO Brad Campbell. Brad?
Thanks a lot, Anupam, JP Morgan, for hosting us. It's great to be here. It's always a great way to start the year. Everybody's been reflecting on how nice it is to have sunshine outside, a better macro environment. It's a good time to be a biotech CEO with two commercial products. And we'll talk a lot more about Amicus. Of course, we'll be making forward-looking statements, so I'll refer you to our safe harbor provisions. Amicus Therapeutics, we are a company that was founded on the idea that we could make next-generation therapies for people living with rare and orphan diseases.
And after almost 20 years with the company, I think what you'll see today is we've really differentiated ourselves. We have built a real sustainable business here, poised to create real value for our shareholders, but it all starts with creating great medicines for patients. And our vision is to become a leader in the rare disease, drug development space. And I think we're really in a place of transition this year, that puts us on a trajectory to do that. So what is the business of Amicus? We have two commercial products today, and we'll talk a lot about, Pompe disease, Pombiliti and Opfolda, which, of course, was all the rage coming into the end of the year, last year with our approvals.
But we do have a significant and growing product in Galafold for Fabry disease. That's the core of our value today, and so you'll see significant growth from both of those products, and I'll talk more about that over the course of the presentation. Just a couple other things I'd orient you to here. We are a global business. I think that's really important because the leverage we get from the investment we made in the Galafold infrastructure leads to significant opportunity to drive profitability for the first time for Amicus.
And for the first time, we will deliver a full year of non-GAAP profitability this year, and that's all because of that investment we made in Galafold, and now all of the revenues that come in from Pombiliti and Opfolda help contribute to that evolution of our financial structure. We do have, as I said, two commercial products. We are just at about $400 million in combined sales at the end of the year, last year. That's a 21% increase over the year prior, and you'll see significant growth again this year and going forward. And both of those products, both Galafold and Pombiliti, Opfolda, have about $750 million-$1 billion in revenue potential for each product.
So that looks like a $2 billion potential peak opportunity for our portfolio today. 2023 was certainly a transition year. We saw significant, again, revenue growth for Galafold. We started the year thinking we could do 12%-17% year-on-year growth. We actually raised that to 16%-18% and delivered just above 17% growth for those products. Of course, we got the approvals of Pombiliti and Opfolda. We don't have to talk about inspection risk here today, for those of you who've been part of the story for a long time, or even for the last year.
Had great launches, and we'll talk a lot more about the launch color, what we're seeing, why we're confident in the opportunity, going forward. We did work on in a very limited way scientific research into our next-generation Fabry Pompe gene therapy, as well as our next-generation Galafold product. And we'll continue a very modest investment in that this year as well. But all of that was with an eye towards turning profitable. We committed to do that in the fourth quarter, and what we've said is we're on track to do that.
Of course, we still have to close our books, but you'll see the outcome of that, as we get to our full year, year-end call, over the next, month and a half or so. We've talked a lot about this, you've followed this, but it was kind of a year of headlines for us. Continue to see growth in Fabry. In fact, we were the fastest-growing treatment on the market for Fabry disease. A successful launch. We're gonna talk a lot more about that. We passed $100 million in quarterly revenue for Galafold for the first time last year, and you saw that again in the fourth quarter as well.
And that was really driven by significant patient demand, and I'll talk about some of the dynamics that we're seeing in the Fabry market that gives us continued confidence there. We did refinance our debt, which, which I think was really important in the context of, of just pushing out those payments, lowering the interest payments, and ensuring that we could really maintain our independence of the equity capital markets from an operating perspective. And then, of course, continue to show exciting data coming out of the ongoing extension studies for Pombiliti and Opfolda.
This year will be a pivotal year for Amicus. Again, we know we can continue to grow Galafold. We think we can do 11%-16% year-on-year growth, and that's on a much larger base, of course, than we did the year before. So continue to grow that product robustly. We'll continue the launches of Pombiliti, Opfolda. We'll do a little bit of work around the portfolio, as I mentioned, but the vast, vast majority of our R&D expense goes into continuing to expand the labels for Fabry and for Pompe, our ongoing clinical work. We have about 95 patients still on clinical drug today on Pombiliti, Opfolda, and we'll talk about sort of how we think about converting them.
And we'll continue to maintain our leadership position from a medical and development perspective in Fabry and Pompe disease. And all of that while delivering on our first full year of non-GAAP profitability. And again, I think that really differentiates us from most of our peers in this space. So let's talk a little bit more about Galafold. Most of you know of the disease. It's a lysosomal storage disorder. It affects primarily the heart, CNS, and the kidneys. If people aren't treated for their Fabry disease, eventually they'll die from one of those organ systems, typically.
What's, I think, important about Fabry, and this will permeate the conversation as I go through, is that it was once thought of as a disease that primarily affected men. Over time, what we've realized is though although it's X-linked, women have disease progression as well. Women, in fact, make 50% of the treated population today. This is one of the most underdiagnosed genetic diseases, and this market, therefore, will continue to grow significantly over time. So what does that look like? Today, this year, at least 2023, we believe we passed the $2 billion mark in terms of global sales.
By the end of this decade, we think that'll be $3 billion in global sales for treatments for Fabry disease. You can see that dark blue bar on the bottom of those bars is the percentage of patients who have an amenable mutation. So you could see today, we're looking at about $750 million worth of treated amenable patients. Then we think by the end of the decade, that will be well over $1 billion. The market will continue to grow. Why is that? It's growing because we're just finding more Fabry patients, and there are a few things that have led to that.
I think first and foremost is just the availability of low-cost genetic screening. And so we've been able to drive that down, which means that more physicians and more patients can get access to that, to that technology, in a much more prevalent way. We've also seen newborn screening in a very sort of targeted way, not as prevalent as Pompe, which I'll talk more about, but certainly, that helps to identify families who have Fabry disease. And remember, once you find a Fabry patient who has undiagnosed disease, you typically find three to five additional family members who also will be undiagnosed with the disease.
So this is a hugely growing market, fueled primarily by, by diagnosing patients. Galafold is the fastest-growing product used within this market. So just to put a fine point on that, how has this market evolved just since we've launched Galafold? So back in 2015, the year ahead of launch, for Galafold, there were about 10,000 diagnosed patients worldwide. About half of them were on treatment, and of course, all enzyme replacement therapy. In 2023, that number has almost doubled. The number of treated patients has more than doubled, so there's 11,000 now, patients who are treated for Fabry disease.
We represent 2,400 of those patients. But unfortunately, there's actually a higher number of diagnosed, untreated patients. So there's 6,000 patients now who are diagnosed and untreated. Many of them will be eligible for treatment with Galafold. In fact, an interesting phenomenon is that the vast majority of new patients who are diagnosed with Fabry have an amenable mutation. So we think as we diagnose more and more Fabry patients, more of them will be eligible to come on our therapy. So let's look at Galafold specifically in the year in review, and then I'll talk about the year going forward.
So as I mentioned, great growth year for us from a sales perspective, delivered $388 million in global sales. That was, again, over 17% year-on-year growth, at a constant exchange rate. I talked about the 2,400 patients. Big number. We'll continue to see that grow over time. But importantly, too, on the upper left-hand side here, you can see a market share of treated amenable patients of 60%-65% globally. Now, the good news is, that means there's a lot more patients still to treat and to put onto therapy, but you can see that we're continuing to penetrate into that treated amenable market, and we'll continue to do that over time.
Now, over 40 countries that have a reimbursement and regulatory approvals for Galafold, and you'll see that grow over time as well. So, what do we expect going forward? The answer is continued, strong, robust growth. How is that going to happen? Well, we continue to look at improving diagnosis, medical education. The more patients we can find, the more patients are eligible for treatment, whether it's for Galafold or one of the other products. But you'll see that continue to happen. I'll talk a little bit about one specific strategy here in a minute.
The other piece is just market share of treated amenable patients. You heard me say we got 60%-65% global share today. So what we see in our most mature markets is that we can get that up to 85% or 90% of share. So we know that that's kind of the target for how high we can bring our global market share. But a huge part of the growth is coming from finding new patients and penetrating into the diagnosed, untreated population. 1,000 of those 2,400 patients actually were naive to treatment before they came onto Galafold. So we are growing the market.
We expect to continue to do that. And in fact, we saw this year, the highest net new patient growth in places like the United States, United Kingdom, Japan, since launch. Since the first full year of launch, I should say. And where is that growth coming from? In those markets, it's primarily from new patients, naive patients. That's what we had envisioned happening. If you think back to that pie chart that I showed you over time, as this market evolved, and that's exactly what we're seeing, and we expect to continue to see that.
We will see a little bit of a benefit of geographic expansion. I know that's something we'll touch upon in the Q&A. There are still some markets in Latam and in Asia Pacific, where we're either newly reimbursed or expect reimbursement. There's maybe 15% of patients remaining in those markets, so that'll help a little bit as well. But all of that is buoyed by this 90% adherence and compliance. We've seen that since launch. It's one of the best adherence compliance rates I've seen in any small molecule for many treatments, frankly.
That's something that says effectively, when patients start on therapy, they stay on therapy, and so we tend to have them for as long as they're treated. One last thing that I'll touch on in the context of Fabry disease is artificial intelligence. It's obviously a buzzword today. Not trying to get the AI premium here for Amicus, but I do think that AI will transform drug development, biotechnology, healthcare broadly. You're already seeing it in drug discovery, you know, high-throughput drug discovery approaches. You saw that in probably the development of the mRNA vaccines, the COVID vaccines.
You'll see that in drug development, designing the studies, a whole host of other areas. But where we think it can be the most relevant impact for us today is in diagnosing patients. You heard me talk about the improvement in diagnosis globally. What we're talking about here is a partnership with a company called OM1. We use machine learning, along with some physicians, to develop a better diagnostic algorithm for Fabry disease. And now we're piloting that in a closed system with significant end-to-end payer claims, electronic medical records, in a very large, millions of lives, Mid-Atlantic healthcare system.
We're gonna push this program into that. Number one, of course, it helps to prove that you can do it with the new algorithm. But number two, you're gonna find a lot of Fabry patients, and again, they're gonna have 3-5 family members who are undiagnosed with Fabry as well. Excuse me. So we think, number one, this is important just to help prove the theory, but also we think this will help continue to drive real outcomes. And then you have treatment options for these patients. So look out for more news for that. So again, healthy, growing product opportunity.
Really excited about the business there. So now let's talk a little bit about Pombiliti and Opfolda. The top line message is, really pleased with how the launch is going so far. Such a long time coming. Complicated drug development as it always is. This is a tough disease. It's a neuromuscular disease. It's a lysosomal storage disease. If left untreated, patients will die typically of progressive, respiratory failure or pulmonary, outcomes. Of course, you have the infantile flavor of the disease, which also has a significant cardiac component to it as well.
I think important to highlight here is this is now an over $1.3 billion market today, for primarily, aside from our little contribution, primarily the existing enzyme replacement therapies. And what you see in the next slide is that just like Fabry disease, this is a largely growing market. We think it'll be $2 billion by the end of this decade. It's over $1 billion, actually $1.3, as I said today. You can see the geographic split. This is a little bit different than some of the other LSDs because it's such a high pricing disparity between the United States and Europe and the rest of the world.
So the predominant treated population comes from those three geographies, or at least sales does. It's about 4,000, we think, adults treated today with Pompe disease, with one of the enzyme replacement therapies. So large and growing market, fueled by newborn screening in the United States and some other geographies, again, but also fueled by low-cost genetic testing. If you look into populations with muscular dystrophy or with elevated CK, you find a very enriched population for Pompe disease. It's sort of the fourth or fifth most common disease that's identified through these screening opportunities.
That's driven this kind of, you know, low double-digit growth rate for a long time in this market, and we'll continue to see that going forward. All that being said, we know, and this has been well documented, that the legacy enzyme replacement therapy, well-published, was unfortunately most patients come onto that therapy and after a year or two, plateau, and then over time, starts to decline. That's been well-documented, well-studied. Huge need for new therapies. And what we designed was a very differentiated approach to treating this disease.
What we knew is that a big challenge with legacy enzyme replacement therapy was it was poorly phosphorylated. Of course, mannose-6-phosphate, for those of you who haven't followed the story, is what's critical for getting this enzyme taking up into key tissues of disease, particularly in the muscle. What we were able to do is select a cell line that had high amounts of mannose-6-phosphate that was produced naturally, and then we built our manufacturing process around that. The importance of that naturally occurring carbohydrate is that GAA within the cell has to be processed down to a more mature form in order to optimally turn over glycogen.
So this is a very differentiated approach, and we preserve those properties of this enzyme replacement therapy in order to lead to that. So there's a mechanistic difference between the way we address that carbohydrate challenge and the way, and the way our competitor did with their next generation product. The other thing, of course, is that these enzymes aren't very stable in the circulation. These are long infusions. These enzymes aren't typically meant to be in the blood for a high, long amount of time. By including the enzyme stabilizer, we add additional stability and provide for more active enzyme to be taken up into the tissue.
Very different mechanism of action. What that led to was a very differentiated clinical outcome. What you see here is a summary of our phase III data, our pivotal data from the PROPEL study, which showed that in particular in this graph, in patients who were experienced, that is, they were on enzyme replacement therapy coming into the study. If you compare head-to-head, in these experienced patients, we're the only product that was able to show improvement. In particular, this is showing six-minute walk in these patients.
These patients were on drug for an average of seven and a half years, right? They're clearly in that decline phase, if you look at the natural history. We don't just keep them stable, we can actually improve them. And the important thing is that then translated to, in particular, the label of the United States that said, "For patients not improving on enzyme replacement therapy, we can deliver these outcomes." So we really see this as an opportunity to reset expectations for physicians and for patients, and what they want to get out of their therapy.
First time this has ever been shown, and this is really the data that we think is driving the clinical differentiation in this disease. So how's the launch gone? The answer, top line, again, is incredibly well, very pleased with what we've seen so far. Last year, we delivered $11.6 million in global revenue. The guidance we gave sort of in the middle of the quarter was we hoped to do about $10 million, so we outperformed that guidance that we gave middle of the quarter. Importantly, 120 patients on treatment or having scheduled to get on treatment.
That comes from two sources. 105 of them were clinical trial patients or expanded access patients, so a nice bolus of patients that we focused on immediately to convert to therapy. And then 15 new patients spread across each of the three geographies about equally. But what's really important within that segment is that we're seeing a significant number of switch patients in the United States. Still early days, small numbers, but significant numbers of switch patients coming from Nexviazyme. In fact, the majority in the United States came from Nexviazyme.
Then in Europe, we're seeing a mix of Myozyme, Nexviazyme, or sorry, Lumizyme, Nexviazyme, and then naïve patients as well. So all the patient segments that we wanna see are represented there. Great outreach with KOLs. We've seen all the top doctors. We'll continue to interact with them in those three countries, and then as we start to launch into other countries. Pricing and reimbursement has gone incredibly well, both in the United States and in Europe. And we'll talk more about this, I think, in the Q&A, but we do have a number of new countries that we think will launch into this year, primarily in Europe, and those countries will likely mostly come in the second half of this year, 2024.
Just to drill down a little bit into the two regions, so Europe, and we've lumped U.K. in with Europe, although technically not part of the EU anymore, but those have gone incredibly well. There's about 1,300 treated patients in Europe. There's another 200 patients who are estimated to be treated in the U.K. Importantly, you saw it today, I think they published on their website, and we had talked a little bit about this. We are the fastest-ever product to go through the NICE reimbursement process. We're the first product ever to be recommended for reimbursement by NICE in the U.K. prior to marketing authorization.
I think that just shows the acknowledgment of the value that they think we can bring, both in terms of the profile of the product, so efficacy and safety, but also the pricing strategy, which we've talked about many times, which is we price for access, which means parity or modest discount. I think that's a great demonstration of probably one of the strictest healthcare authorities in the world supporting reimbursement for our product. One other factor that we've shared today is that, so between the EAMS patients and then the new commercial patients in the UK, which effectively means we've been available for about two years because EAMS came about a year and a half before we launched in the UK.
We're at a 30% market share in the U.K.. So if you think about how does this product perform over about a two-year period, we think that's a great example of what it could do. If you drill down in the U.S., in the U.S., there's about 800 patients we estimate about 800 patients treated, about 80% of them are adults. It's about a $500 million market opportunity. Very, very clearly the largest single market. We've seen great uptake, as I mentioned, both the EAMS conversions and the new commercial patients. And I think, again, most importantly, one of the biggest questions coming into this launch was.
Okay, especially in the U.S., where Sanofi launched their next-generation product about two years ago, would you be able to switch patients from that product, or would they be stuck? And what we're seeing, again, it's early days, relatively small numbers, but very clearly the majority of patients, all but one, switching off of Nexviazyme for the new commercial patients, in the United States. So really positive initial feedback from patients and physicians. I would say look out in coming congresses for some of the case studies.
You know, these are... What we're hearing from patients and physicians is very positive experiences coming onto the drug, and we'll start to publish on that, and then we can share that, more broadly. But I think for all of our metrics, this has been an incredible launch. It sets us up for a great trajectory going forward. The only other thing I would say there, though, is I think the most important metric for us to look at is the number of patients on drug at the end of this year. That means we'll have a full year of launch under our belt.
We'll see what shares we've been able to get to in those three key markets: U.S., Germany, and the United Kingdom. It will be a significant amount of revenue, for sure, and you can see that in the commitment now to full-year profitability. So no question, this will increase our revenue growth. But I think the most important metric for us to focus on is number of patients that we get on the drug, and we look forward to continuing to do that over the course of the year. From regulatory clinical perspective, and I know we want to get to Q&A, so we only have two more slides here.
Continue to submit reimbursement dossiers. 10 of them have been submitted. Probably two-thirds, three-quarters of those will get to reimbursement this year. Continuing to expand the indication opportunity in late-onset and infantile-onset Pompe, and we do have an ongoing registry, which will, we think, eventually lead to real-world evidence, which continue to differentiate the product. Two other quick things. The first is, again, I think we are a very unique company in the biotechnology, rare disease space, in particular, in kind of the midcap space.
Two very unique therapies. One already demonstrated it's a real, growing important product. Another one, great early read on the launch. Huge opportunity, combined opportunity of $1.5 billion-$2 billion between those two products. Full-year non-GAAP profitability this year, and then clear line of sight to positive free cash flow. So I think really differentiated company. And you've heard us talk about this before, and I wanna sort of close the loop here. So at the end of the day, we think the ultimate measure of success is the number of patients that come onto our drug.
Of course, that's part of our mission, but to me, that ties back exactly to building shareholder value. Why is that? The more patients we get onto drug, the more revenues we can produce. The more revenues we can produce, the more profitability we have to invest back in the business, and that's the virtuous circle. To me, that's how you drive shareholder value, and that's how you make a difference in the lives of so many patients. With that, I'll conclude. Thanks a lot for your time, and Anupam will turn it over to questions.
Cool. Thanks so much, Brad. Just for those of you who wanna ask a question, there's three ways to do it. There's the old school method. Just raise your hand, and I'll call on you. There's the new school method. If you have access to the portal, write your question in. It'll show up on this iPad, and I'll ask it for you. I guess there's an intermediate strategy where you email me the question, and I will read it. So, with that, I will kick it off. Brad?
Yeah.
I did want to ask you about your Pompe. You know, give us a sense of what are the key regions that could come online?
Sure.
In 2024, beyond your big three?
Sure. I'm going to ask the management team to variously sort of chime in here. So maybe, Sebastien, you want to take the first one on the pricing reimbursement?
Happy to take this one. So we think our goal is to have launched the product and have pricing and reimbursement completed in over 10 markets by the end of the year. You know, some of these launches will take place in the first half of the year, Nordic countries, Spain, but most of them will actually take place in the second half of 2024. So some of the other EU top five markets like Italy, France, and some of the Benelux markets as well.
But you'll probably have, you know, sort of the majority of the large markets having pricing and reimbursement by the end of the year, this year in Europe.
Questions from the audience? Maybe drilling down a little bit specifically on those 15 patients that were not from the clinical trial experience. You gave a number of metrics that suggested that there, there's naive patients, there's switches from Nexviazyme. Are they coming from certain centers, or is it a trend that you're kind of seeing from all over globally?
Yeah. So it's pretty spread out, which is great. That's what you want to see. Primarily from physicians who had experience through either the clinical studies or the expanded access programs. But of course, those are the key treaters, so that's who you want to be, you know, on the leading edge of your prescribing when you launch the product. I would clarify, just for, you know, for completeness, the naive patients are coming from Europe. Of course, in the United States, we're a switch label. In Europe, we're both switch and naive.
But again, that's what we would expect, and I think the most important thing for us was in the U.S., in particular, where Sanofi had launched their next generation product two years ago. The question is like, would those patients be stuck on that new therapy for some period of time and therefore slow down the launch? And, as I mentioned in my formal talk, the majority of the U.S. patients actually came from that next generation product, which is great.
Whereas in Europe, where we're effectively launching kind of head-to-head with the next generation product, there might even be some markets where we actually get out ahead of them, TBD. But there, we're seeing, I think, a mix across each of the three and more really coming from Lumizyme, and that's because that's the most available patients to switch from. So I think it's playing out kind of exactly as we'd hoped.
In the U.S., maybe you could speak to the label a little bit, right? Because these Nexviazyme switches, are they coming from patients who are progressing or not deriving benefit? You see what I'm saying?
I do. I do. And I think that's, you know, one of the reasons we negotiated for that language, "not improving," and we've seen this as we've had advisory boards, as we look at the patients that we're seeing come onto the drug today. Again, it's early days, but it's exactly that. The progressing patients is fairly obvious, right? So they've, if they've tried Lumizyme and were progressing, and then they tried Nexviazyme and progressing, I think those, if that's a more obvious choice for a physician. Where the real win comes is we estimate about 50% of patients are... would have historically been seen as stable.
But if you really kind of peel back the onion a little bit, what you find is, number one, if you look at their fatigue or pain or, respiratory assistance, it actually, many of them are subtly getting worse, and so there's an opportunity to, to treat those patients. But really, the standard should be: Are they improving? And if they're not improving, then you have an option which has been shown to improve these patients across a variety of measures. And so what we're seeing is a little bit of both today on Anupam, but I think how we win in the end, how we become the lion's share, the standard of care, is we really are able to demonstrate improvement in those kind of historically seen as stable patients.
Yep. Question from the audience?
There's a big lysosomal storage disease meeting in February.
Yes
Called World. Could we get some of those case studies that you mentioned in your talk at that conference?
Yeah. You should expect to see that in particular from one of our leading physicians. There was historically during EAMS one center, Cambridge, in the U.K., where they had treated a large cohort, I think 12 patients, during the EAMS program. They had done a poster doing some of their patient outcomes as well, so that's already in the literature. Folks should take a look if they're interested, but yeah, you should see some of that new data at the World Conference.
And this will specifically focus on patients who are on Nexviazyme switching to AT- GAA or?
In the case of the UK experience, I don't... It's either going to be Lumizyme switchers or Nexviazyme switchers.
Okay.
I don't know which right now, but it'll be switch patients.
Okay. Questions from the audience? And then maybe switching gears a little bit to Galafold. You did, in a press release, I think yesterday, give some guidance around growth of constant, I think it's 11%-16% at constant-
That's the guidance. That's right.
Yeah, is the guidance for a year, which I think roughly translates to $430-$450 for the year.
Yep.
I'm looking at Andrew-
Right.
because I can't really do math.
Right. Yeah. Let's do math on the fly.
Yeah. You know, what are... You mentioned this in your talk a little bit. What are some of the higher growing countries that underpin that guidance?
Yeah. Sebastien, you want to talk about what we're seeing-
Yeah.
From a Fabry growth perspective?
So maybe first point is the U.S. had a phenomenal year this year. You know, the number of new patients start was actually even better than our first full year of launch in the U.S. So we had growth above 20% in the U.S. market alone. That's the number one market for us, for the Fabry market overall. The second, you know, best performing market was Japan. And so, Japan, again, we grew more than 20% last year. You know, strong, strong demand. Lots of naive patients also being identified in Japan. And then some of the more core E.U. markets continue to show healthy, healthy growth.
This is a result of more and more naive patients being captured. In some of these markets, we have, you know, 80%-90% share of amenable patients. So the growth is really, really driving by newly identified patients. And we've come to a point where in those markets, we've really established Galafold as the standard of care for those patients with amenable mutations. And so every new patient diagnosed with Fabry disease and amenable mutation is put on Galafold.
And then from a country perspective, the new ones that we're seeing-
Yeah.
You have those three core countries that will continue to grow, our core regions. And-
Yeah. So beyond those, we've, you know, we continue to add markets from a pricing and reimbursement. One of the big milestone this year was the addition of Taiwan, where we even managed to get Galafold reimbursed as first-line treatment for patients with amenable mutations. So this has recently been launched in the fourth quarter last year. We've got a few small countries in Eastern Europe, European markets. I think Hong Kong, Singapore would be next. One of the remaining sizable markets where we are in the midst of pricing reimbursement is Turkey.
Turkey is a sizable market in terms of number of patients. This is roughly equivalent to any of the EU five markets. Average price is lower than those markets, but still a sizable opportunity for us, and we hope to get reimbursement in 2024.
I think that's part of why we're so bullish here, is that, yes, we have geographic expansion, yes, we have, you know, new countries where we're more recently launched, but you're still seeing the most growth coming from the largest countries. And that's, again, a reflection of the dynamic of the Fabry market, which is we just keep finding more and more patients. And, you know, you refer back to that pie chart, where there are more diagnosed, untreated patients today than there were when we launched in 2016, and that's in the backdrop of doubling the number of treated patients.
Lots of room to continue to serve these patients.
Questions from the audience?
What steps is Sanofi taking that you may be aware of to ensure that patients stay on their suite of the two drugs approved?
Yeah, you know, don't wanna put words in competitor's mouth, but the probably the biggest things that we hear are the obvious one, which is, you know, length of time on therapy. You know, Lumizyme's been out there for so long, the first-generation ERT. But of course, now they're trying to switch all the, you know, first-generation patients to patients on the first generation drug to the second generation drug. So that sort of flies in the face of that a little bit. There's another component around a two-component therapy.
So of course, we have the enzyme stabilizer. We've talked about why that makes a difference. We'll continue to educate on that. But I think, you know, just from a competitive perspective, it's simple to stay on one medicine. And at the end of the day, it's the data, right? So if you look at the data, we think our data is differentiated. We know we're the only product that's shown improvement in those experienced patients. And so, you know, I think that's what drives the story at the end of the day. I think we have differentiated ourselves from a, I think, a partnership perspective.
We get a lot of feedback from physicians in terms of the scientific rigor, the conversation with physicians, the way we support the transition process, which can be complicated, moving from one therapy to another in the space. I think we've established a reputation of trust within the physician community, and I think that helps as well.
Any final question? Oh, yep, go ahead.
Can you say a little bit about investments you're making in preclinical programs?
Yeah. Maybe, Jeff, talk a little bit about sort of what the strategy is there and the small investment we're making. Yeah. So we're making very targeted, judicious investment in our preclinical pipeline, really focused on Fabry and Pompe, so we have very novel engineered transgenes for Fabry and Pompe. We're looking at various ways to deliver those, either AAV or non-viral approaches. So, you know, we have Fabry and Pompe genetic medicines, and we have some really compelling proof of concept data showing the potency of those engineered transgenes versus a typical wild type transgene.
We also have next generation Fabry chaperone program as well. So our strategy really right now is to, first of all, focus on growing Galafold, launching Pombiliti Opfolda, and, you know, focusing on profitability. So it's really trying to just position ourselves for the future to have something from that early pipeline that we're very excited about, that could, you know, really make a difference in terms of how that product profile would look to deliver the right efficacy in a safe way with the right cost of manufacturing. So right now, we're sort of in optimization stage before we'd really full bore invest in bringing one of those into the clinic.
And, you know, once we move down the path on profitability and can fund that research, we'll look to do that, you know, as one of our ways to grow the portfolio. One thing you saw, it didn't get a lot of attention, is we did. So you remember, we've increasingly downsized our investment in gene therapy broadly. We had wound down a number of our programs, we found some homes for some of them in different places. We did finally give back the rights to our Batten program, CLN6, CLN3, which was the legacy clinical studies that we had ongoing to Nationwide Children's Hospital.
Our hope is that Patient Foundation will be able to bring those forward in some way, but that was the last piece of sort of the vestige gene therapy that we wound down at the end of last year. And as Jeff said, I think, look, we always want to be leaders in the Fabry and Pompe space. Very, very modest investment in those programs today. The idea would be, you know, 2025, when we're generating positive free cash flow, and we can fund it on our own dime, then it might be prudent to bring either something from that portfolio or, or, you know, something else that might come along into the clinic.
But for now, that'll. You know, the vast majority of our R&D spend is on ongoing studies for Pompe, registry commitments for Fabry, and investment in next-generation manufacturing for Pompe, for Pombiliti.
All right, Brad and team, thanks so much.
Thanks, Anupam. Thanks, guys.